FibroSURE

The stage of fibrosis is the most important single predictor of significant morbidity and mortality in individuals with hepatitis C and other chronic liver diseases. Investigators have sought a noninvasive alternative to liver biopsy for both as an initial assessment and then as a monitoring tool to assess response to therapy. A variety of laboratory tests have been proposed as an alternative to liver biopsy. The most highly marketed test in the United States is FibroSURE, which is marketed by LabCorp.

Three different FibroSURE tests are available. HCV FibroSURE uses a combination of six serum markers of liver function plus age and gender in a patented algorithm to generate a measure of fibrosis and necroinflammatory activity in the liver corresponding to the METAVIR scoring system for stage of fibrosis and grade of necroinflammatory activity (NI). The serum markers include measurements of alpha-2 macroglobulin, haptoglobin, gamma glutamyl transpeptidase (GGT), ALT, and apolipoprotein A1. Quantitative results of 6 biochemical tests are analyzed using a computational algorithm to provide a quantitative surrogate marker (0.0-1.0) for liver fibrosis (METAVIR F0-F4) and for necroinflammatory activity (METAVIR A0-A3).

In patients with HCV infection FibroSURE has been used to determine liver status before initiation of HCV therapy and six months after completion of therapy. It is also ordered for patients who are at increased risk of complications from a liver biopsy. 

The negative predictive value of a Fibrotest score <0.31 (absence of clinically significant fibrosis) was 85% when compared to liver biopsy in 1,270 HCV infected patients with a 38% prevalence of significant liver fibrosis (F2, 3 or 4). The positive predictive value of a Fibrotest score >0.48 (F2, 3, 4) was 61% in this patient cohort. 

Evidence based guidelines on the management of hepatitis C from the American Association for the Study of Liver Diseases stated: "Although liver fibrosis markers are commercially available, they are currently insufficiently accurate to support their routine use. Until sensitive serum markers can be developed that will define all stages of fibrosis and mirror the information derived from liver biopsy, the procedure remains the only means of defining the severity of damage from HCV infection in many patients".

In a technical review on the management of hepatitis C, the American Gastroenterology Association (2006) stated:"Neither clinical nor laboratory markers, individually or in combination, predict accurately the degree of necroinflammatory activity or the level of fibrosis in the liver. Therefore, despite sampling error, liver biopsy remains the gold standard for determining histologic grade and stage." 

The American Association for the Study of Liver Disease's (2009) updated practice guideline on the diagnosis, management, and treatment of hepatitis C includes a recommendation which indicates current noninvasive tests should not replace the liver biopsy in routine clinical practice.

ASH FibroSURE consists of ten serum markers including ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, haptoglobin, AST, glucose, total cholesterol and triglycerides. A prognostic algorithm is used to report quantitative scores for fibrosis, steatosis and alcoholic steatohepatitis. NASH FibroSURE includes the same ten biochemical assays as ASH FibroSURE but the algorithm is used to calculate scores for fibrosis, steatosis and nonalcoholic steatohepatitis.

The performance characteristics of FibroSURE have been  determined by LabCorp. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Currently, evidence based data do not support the use of these markers. Insurance companies consider this test to be experimental, investigational and not medically necessary. 

HCV FibroSURE should not be ordered if patients have any of the following conditions: Gilbert Disease, acute hemolysis associated with ribavirin therapy, acute hepatitis, extra-hepatic cholestasis, transplant patients, and/or renal insufficiency patients. Any of these clinical situations may lead to inaccurate quantitative predictions of fibrosis and necroinflammatory activity.

Specimen requirement is 5 mL of blood drawn into a plain red-top tube or gel tube. Serum should be separated from cells within 1 hour and frozen in two plastic screw-capped tubes for transportation. All FibroSURE tests are performed and interpreted by LabCorp.

References

Eiswerth MJ et al, In Lieu of Biopsy: A Review of Noninvasive Liver Disease Assessments, Gastroenterologist Endoscopy News, August 2025, Gastroendonews.com, pages 1-8.

Grady JT, Cyrus JW, Sterling RK. Novel noninvasive tests for liver fibrosis: moving beyond simple tests in metabolic dysfunction-associated steatotic liver disease. Clin Gastroenterol Hepatol. Published online May 30, 2025. doi:10.1016/j.cgh.2025.02.035.

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835.